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Background: Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking. Aims: We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center. Methods: We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation. Results: We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28–0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%). Conclusion: Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute‐on‐chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT). Methods: A prospective, randomized, single‐center, open‐label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT). In the hemoadsorption group, the CytoSorb adsorber was incorporated into the CRRT system, replaced after 12, 24, and 48 h, and removed after 72 h. The primary endpoint was the serum bilirubin level after 72 h. Results: CYTOHEP was terminated early due to difficulties in recruiting patients and ethical concerns. Three of 9 patients (33%) were treated in each group. Comparing the three groups, mean bilirubin levels after 72 h were lower by −8.0 mg/dL in the "CRRT with hemoadsorption" group compared to "CRRT without hemoadsorption" (95% CI, −21.3 to 5.3 mg/dL; p = 0.17). The corresponding mean difference between "CRRT without hemoadsorption" and "no CRRT" was −1.4 mg/dL (95% CI, −14.2 to 11.5 mg/dL; p = 0.78). Comparing "CRRT with hemoadsorption" and "no CRRT," it was −9.4 mg/dL (95% CI, −20.8 to 2.1 mg/dL; p = 0.0854). Only 1/9 patients (11%, "no CRRT" group) survived day 30 after study inclusion but died on day 89. IL‐6, liver function parameters, and clinical scores were similar between the study groups. Conclusions: CYTOHEP failed to demonstrate that extracorporeal hemoadsorption combined with CRRT can reduce serum bilirubin in ACLF patients with acute kidney failure. [ABSTRACT FROM AUTHOR]

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival. [ABSTRACT FROM AUTHOR]

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival.

Abstract Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray’s competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000–1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312–1.710, P

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. [ABSTRACT FROM AUTHOR]

Objective To observe the effectiveness and safety of Regional Citrate Anticoagulation (RCA) in CRRT combined with artificial liver treatment. Methods Clinical data of 54 sessions of CRRT linked with artificial liver treatment using RCA in 21 patients with acute on chronic liver failure (ACLF) combined with acute kidney injury (AKI) admitted to our center from December 2019 to June 2023 were collected.. The improvement of liver and kidney function indicators, anticoagulant effect and adverse reactions of citric acid, and patient outcomes were observed and analyzed before and after treatment. Results The 54 cases of liver and renal function indexes were improved, which showed a statistically significant difference (P < 0.05); All 54 cases of CRRT linked artificial liver treatment were successfully completed, and no obvious blood clots were found in the extracorporeal circulation tubing, filters, and adsorbers; There was no statistically significant difference (P > 0.05) in the total calcium and ionized calcium levels of all patients at each stage of artificial liver treatment compared to before treatment; However, three cases of CRRT combined with PE and one case of CRRT combined with DPMAS+LPE experienced citrate accumulation after treatment, which returned to normal after 24 hours of timely correction and supplementation; The 30-day survival rate of the 21 patients was 13 survivors, 5 deaths, and 3 discharged automatically. Conclusion Under strict monitoring and timely adjustment, the application of RCA in CRRT series artificial liver treatment is safe and feasible, and is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a commonly seen condition in the natural course of cirrhosis. The aim of this study was to evaluate the pooled incidence and risk factors of AKI in different clinical stages and situations in patients with cirrhosis. Methods: Search was conducted on 13 December 2023 across MEDLINE (PubMed), Embase, and Cochrane databases. Meta-analysis was performed using a generalized linear mixed model. Results: In total, 73 studies with 5,202,232 patients were finally enrolled in the meta-analysis. AKI commonly occurs among hospitalized cirrhotics experiencing any decompensation event (29%) as well as among stable outpatients (28%) throughout a 1-year follow-up period. On admission, patients with infection or sepsis/septic shock had the highest AKI rate (47%), followed by those with hepatic encephalopathy (41%). Furthermore, the severity of liver disease proved to be a substantial driver for AKI development, while patients at intensive care unit had the greatest AKI incidence (61%). Conclusions: Both hospitalized patients and stable outpatients with cirrhosis exhibited an elevated susceptibility to AKI. Patients at intensive care unit and those with severe liver disease, infection, sepsis/septic shock, hepatic encephalopathy, or acute on chronic liver failure upon admission are at higher risk for AKI. Trial registration: PROSPERO, registered 09/12/23, CRD42023487736 [ABSTRACT FROM AUTHOR]

Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray’s competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000–1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312–1.710, P < 0.001), and sarcopenia (HR 1.802, 95% CI 1.062–3.060, P = 0.029) were independently associated with increased 90-day mortality. Subgroup analysis of male patients with HBV-ACLF revealed that myosteatosis (HR 2.119, 95% CI 1.101–4.078, P = 0.025) was promising prognostic factors for 90-day mortality after being adjusted for ascites, acute kidney injury, AARC score, and sarcopenia. Myosteatosis is predictive of short-term outcomes in male patients with HBV-ACLF. Our results emphasise the importance of focusing on muscle fat infiltration in patients with HBV-ACLF. Further studies are warranted to investigate the underlying mechanisms and potential therapies for myosteatosis. [ABSTRACT FROM AUTHOR]

Summary: Background: Acute on Chronic Liver Failure (ACLF) complicates chronic liver disease (CLD) combining rapidly progressive hepatic with extra-hepatic multiple organ failure and high short-term mortality. Effective therapeutic options are very limited, and liver transplantation (LT) seldom utilised through concerns of high recipient mortality and resource use. Retrospective reports suggest recent outcomes may have improved, but use of LT for ACLF has not been prospectively assessed. Methods: A prospective programme of prioritised liver graft allocation for selected recipients with ACLF through registration on a new national tier, initiated in May 2021 in all 7 United Kingdom LT centres. Candidates were selected by centre multidisciplinary teams, with inclusion criteria mandating cirrhotic CLD with ACLF requiring critical care (CC) organ support and expected 1-month mortality >50%. Exclusion criteria included age ≥60 years, previous LT, comorbidity or substance misuse profile precluding elective LT. A pilot 50 registrations were planned, with pre-specified futility criteria of a 1-year post-LT survival of 60%. Findings: Fifty-two patients were registered on the ACLF tier, median (IQR) age 46 (39–52) years, ACLF grade 3 (3–3) and Model for End-stage Liver Disease (MELD) 39 (35–40). At registration 32 (62%) required mechanical ventilation, 44 (85%) vasopressors and 46 (89%) renal replacement. Forty-two (81%) underwent LT 2 (2–5) days after registration: 10 (19%) did not. All non-transplanted died at median 7 (4–13) days after registration (p

Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. Due to the recipients' generally poor pre-operative clinical conditions and extensive surgery, post-LT respiratory disorders are very common and significantly contribute to related morbidity and mortality. We report the case of a 49-year-old patient with ACLF grade 3 who has been taken care of by the Respiratory Physiotherapy Team since hospital admission. After the extubation, the patient was supported with non-invasive ventilation and mechanical in-exsufflation; meanwhile, early resistance and functional training were started. No adverse events occurred during physiotherapy sessions, and the patient returned home without respiratory support. Respiratory and physical therapy in the intensive care unit after LT were safe and feasible interventions for this patient. Given the high incidence of postoperative pulmonary complications and the high rehabilitation needs, we suggest that physiotherapy should be provided for ACLF recipients.

BackgroundIn trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States.MethodsThis prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections.FindingsThe study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim.InterpretationThis phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone.Fundingwas provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

Background. Acute on chronic liver failure (ACLF) is a severe form of liver cell failure with high mortality rates. Hepatocyte cell death in ACLF can occur through necrosis or apoptosis. The M30 fragment of caspase-cleaved-cytokeratin 18 is a marker of caspase-mediated apoptosis. Objective: To assess serum caspase-cleaved CK 18 (M30) level as a diagnostic marker for acute-on-chronic liver failure (ACLF) in chronic hepatitis C cirrhosis patients. Furthermore, to determine the optimal cut-off level of serum caspase-cleaved CK 18 (M30) for diagnosing ACLF and its association with ACLF severity. Methods: The study involved 60 chronic HCV cirrhotic patients with ACLF (Group 1), 15 chronic HCV compensated cirrhotic patients (Group 2), and 15 healthy controls (Group 3). Laboratory tests and radiological assessments were conducted, including calculation of Child– Pugh score, MELD score, Consortium Liver Failure-Organ Failure (CLIF-OF) score, and CLIF-C-ACLF score using the EASL calculator. Serum level of caspase-cleaved CK 18 (M30) was measured using ELISA. Results: The serum level of caspase-cleaved CK 18 (M30) was significantly higher in group 1 compared to groups 2 and 3. Serum caspase-cleaved CK 18 (M30) showed a high predictive value for ACLF. At a cut-off level of 3.45 ng/ml, caspase-cleaved CK 18 (M30) had a sensitivity of 85% and specificity of 93.3% and AUC of 0.902 (95% CI = 0.833–0.970). There was a positive correlation between serum caspase-cleaved CK 18 (M30) levels and CLIF-C-ACLF score, indicating its potential as a predictor of ACLF severity. Conclusion. Serum caspase-cleaved CK 18 (M30), at cut off value of 3.45 ng/ml can accurately predict acute-on-chronic liver failure in patients with chronic HCV cirrhosis. Higher levels were associated with increased ACLF severity and mortality. [ABSTRACT FROM AUTHOR]

(1) Background: Critically ill patients are frequently diagnosed with pulmonary Herpes simplex virus-1 (HSV) reactivation, which then can lead to HSV bronchopneumonitis and is associated with higher mortality and longer mechanical ventilation. For the particular subgroup of critically ill patients with acute on chronic liver failure (ACLF), however, the impact of HSV reactivation is unknown. We investigated the impact of HSV reactivation in these patients. (2) Methods: We conducted a retrospective analysis, evaluating data from 136 mechanically ventilated patients with ACLF between January 2016 and August 2023. Clinical parameters were compared between patients with and without HSV bronchopneumonitis. (3) Results: 10.3% were diagnosed with HSV bronchopneumonitis (HSV group). Mortality did not differ between the HSV and non-HSV group (85.7% vs. 75.4%, p = 0.52). However, the clinical course in the HSV group was more complicated as patients required significantly longer mechanical ventilation (14 vs. 21 days, p = 0.04). Furthermore, fungal superinfections were significantly more frequent in the HSV group (28.6% vs. 6.6%, p = 0.006). (4) Conclusions: Mortality of critically ill patients with ACLF with HSV bronchopneumonitis was not increased in spite of the cirrhosis-associated immune dysfunction. Their clinical course, however, was more complicated with significantly longer mechanical ventilation. [ABSTRACT FROM AUTHOR]

Introduction: Acute on chronic liver failure (ACLF) has been a difficult entity to define. The use of the hepatic venous pressure gradient (HVPG) for the measurement of portal pressure is well established in chronic liver disease. This is based on data showing that improvements in the HVPG are associated with improvements in clinical outcomes. Methods: The study was a prospective observational study conducted in the department of gastroenterology of a tertiary care center in Northern India for 2 years. Thirty cases each of ACLF (Group I), compensated cirrhosis (Group II), and decompensated cirrhosis (Group III) were enrolled. We evaluated the role of HVPG values and complications in patients with liver disease. Results: The mean age of the cohort was 44.2 ± 7.3 years. The most common etiology of ACLF noted in the study was alcohol (54.4%), followed by infections by hepatotropic viruses (22.2%). ACLF has high short-term mortality compared to compensated and decompensated cirrhotics. Compensated cirrhosis is associated with the lower risk of bleed. The model for end-stage liver disease score was higher among the patients of ACLF (25.2 ± 3.1) and decompensated cirrhosis (23.93 ± 2.8) than compensated cirrhotics (9.7 ± 1.8). The mean HVPG was 12.3 ± 7.5 mmHg, which was significantly higher than the normal gradient. It was also noted that the HVPG was significantly higher in the ACLF and decompensated cirrhotics. Conclusions: HVPG monitoring is recommended in ACLF and decompensated liver disease at admission to stratify the risk of early mortality.

Background Chronic Liver Failure Consortium (CLIF-C) ACLF score, Model for End-Stage Liver Disease (MELD), MELD-Na, and Child-Pugh (CTP) are established scoring systems for predicting mortality in Acute on Chronic Liver Failure (ACLF) patients. However, their comparative accuracy, especially in rural care settings, still needs to be explored. This study aims to assess and compare the predictive performance of these scoring systems, providing a nuanced understanding of their applicability in a tertiary rural care hospital. Method This prospective observational cohort study will be conducted at Acharya Vinoba Bhave Rural Hospital, following approval from the institutional ethical committee. ACLF patients aged 18 and above, presenting within one week of onset, will be included. Data collection will involve comprehensive assessments, including scoring system calculations, clinical examinations, and relevant investigations. Statistical analyses, encompassing descriptive statistics, comparative analyses, survival analyses, and multivariate models, will elucidate the accuracy and independent predictors of 28-day mortality. Expected Outcome Anticipated outcomes include a comprehensive understanding of the strengths and limitations of the CLIF-C ACLF score, MELD, MELD-Na, and CTP in predicting mortality among ACLF patients in a rural care context. The study aims to identify potential correlations and independent predictors, offering valuable insights for risk stratification. These findings are expected to guide clinicians in optimising prognostic assessments and decision-making, thereby improving the care and outcomes of ACLF patients in rural healthcare settings.

Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). A total of 2,063 patients were included (median age 62 [IQR 54–69] years, 38.3% female, median MELD-Na score 26 [19–31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p < 0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p < 0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p < 0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p < 0.001 for all). AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US. [Display omitted] • AKI is common and deadly in cirrhosis, but incidence and outcomes based on etiology are not well described in the US. • Hypovolemic or prerenal AKI is the most common (44%), followed by acute tubular necrosis (30%) then hepatorenal syndrome (12%). • Acute tubular necrosis and hepatorenal syndrome are associated with similar outcomes (∼50% mortality at 90 days). • AKI in cirrhosis is common, but hepatorenal syndrome is uncommon. [ABSTRACT FROM AUTHOR]

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.

The aim of the study was to study the clinical profile of acute on chronic liver failure (ACLF) and establish Cell-free DNA (Cf DNA) as a predictor of the outcome of ACLF. In this prospective study, those patients who fulfilled EASL criteria were included. Cf DNA was estimated in 30 patients and compared with the CLIF-C ACLF score. The median age of 132 consecutive ACLF patients was 40 years. The most common acute insult were sepsis (30.3%) and alcohol (22%). While alcohol (35.6%) and chronic HBV (14.3%) were the most common etiologies of cirrhosis. The overall mortality was 45.5% and 71.2% at 28 days and 90 days, respectively. Multiple regression analysis using the Cox proportional hazard model showed that heart rate (HR 1.06, 95% CI 1.04–1.08 P = 0.001), lung failure (HR 2.82, 95% CI 1.24–6.44, P = 0.02), and cell-free DNA (HR 2.70, 95% CI 1.17–6.24, P = 0.02) were independent predictors of mortality When Cf DNA was used to predict 28-day mortality, Cf DNA was found to have a higher AUC (AUROC 0.84, 95% CI 0.70-0.98, P = 0.001) than the CLIF-C-ACLF score (AUROC 0.81, 95% 0.66–0.97, P = 0.003). However, when 90-day mortality was compared, CLIF-C-ACLF score had a higher area under the curve (AUROC 0.93, 95% CI 0.83–1.00, P = 0.0001) than Cf DNA (AUROC 0.89, 95% CI 0.77–1.00, P = 0.0001). Alcohol and sepsis remain the most common causes of acute insult. Cf DNA is a better predictor of 28-day mortality, whereas CLIF-C ACLF is more accurate to predict 90-day mortality. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Acute-on-chronic liver failure (ACLF) is associated with reduced short-term survival, and liver transplantation is frequently the only therapeutic option. Nonetheless, the post-transplantation prognosis seems to be worse in ACLF patients. Materials and Methods: The databases of two university centers were retrospectively evaluated, and adult patients with cirrhosis who underwent transplantation between 2013 and 2020 were included. One-year survival of patients with ACLF was compared to that of patients without ACLF. Variables associated with mortality were identified. Results: A total of 428 patients were evaluated, and 303 met the inclusion criteria; 57.1% were male, the mean age was 57.1 § 10.2 years, 75 patients had ACLF, and 228 did not. The main etiologies of ACLF were NASH (36.6%), alcoholic liver disease (13.9%), primary biliary cholangitis (8.6%) and autoimmune hepatitis (7.9%). Mechanical ventilation, renal replacement therapy, the use of vasopressors and the requirement of blood product transfusion during liver transplantation were significantly more frequent in ACLF patients. Among those recipients without and with ACLF, survival at 1, 3 and 5 years was 91.2% vs. 74.7%, 89.1% vs. 72.6% and 88.3% vs. 72.6%, respectively (p=0.001). Among pre-transplantation variables, only the presence of ACLF was independently associated with survival (HR 3.2, 95% CI: 1.46-7.11). Post-transplantation variables independently associated with survival were renal replacement therapy (HR 2.8, 95% CI: 1.1-6.8) and fungal infections (HR 3.26, 95% CI: 1.07-9.9). Conclusions: ACLF is an independent predictor of one-year post-transplantation survival. Importantly, transplant recipients with ACLF require the use of more resources than patients without ACLF. [ABSTRACT FROM AUTHOR]

(1) Background: Critically ill patients are frequently diagnosed with pulmonary Herpes simplex virus-1 (HSV) reactivation, which then can lead to HSV bronchopneumonitis and is associated with higher mortality and longer mechanical ventilation. For the particular subgroup of critically ill patients with acute on chronic liver failure (ACLF), however, the impact of HSV reactivation is unknown. We investigated the impact of HSV reactivation in these patients. (2) Methods: We conducted a retrospective analysis, evaluating data from 136 mechanically ventilated patients with ACLF between January 2016 and August 2023. Clinical parameters were compared between patients with and without HSV bronchopneumonitis. (3) Results: 10.3% were diagnosed with HSV bronchopneumonitis (HSV group). Mortality did not differ between the HSV and non-HSV group (85.7% vs. 75.4%, p = 0.52). However, the clinical course in the HSV group was more complicated as patients required significantly longer mechanical ventilation (14 vs. 21 days, p = 0.04). Furthermore, fungal superinfections were significantly more frequent in the HSV group (28.6% vs. 6.6%, p = 0.006). (4) Conclusions: Mortality of critically ill patients with ACLF with HSV bronchopneumonitis was not increased in spite of the cirrhosis-associated immune dysfunction. Their clinical course, however, was more complicated with significantly longer mechanical ventilation.

Introduction and Objectives: Acute-on-chronic liver failure (ACLF) is associated with reduced short-term survival, and liver transplantation is frequently the only therapeutic option. Nonetheless, the post-transplantation prognosis seems to be worse in ACLF patients. Materials and Methods: The databases of two university centers were retrospectively evaluated, and adult patients with cirrhosis who underwent transplantation between 2013 and 2020 were included. One-year survival of patients with ACLF was compared to that of patients without ACLF. Variables associated with mortality were identified. Results: A total of 428 patients were evaluated, and 303 met the inclusion criteria; 57.1% were male, the mean age was 57.1 ± 10.2 years, 75 patients had ACLF, and 228 did not. The main etiologies of ACLF were NASH (36.6%), alcoholic liver disease (13.9%), primary biliary cholangitis (8.6%) and autoimmune hepatitis (7.9%). Mechanical ventilation, renal replacement therapy, the use of vasopressors and the requirement of blood product transfusion during liver transplantation were significantly more frequent in ACLF patients. Among those recipients without and with ACLF, survival at 1, 3 and 5 years was 91.2% vs. 74.7%, 89.1% vs. 72.6% and 88.3% vs. 72.6%, respectively (p=0.001). Among pre-transplantation variables, only the presence of ACLF was independently associated with survival (HR 3.2, 95% CI: 1.46-7.11). Post-transplantation variables independently associated with survival were renal replacement therapy (HR 2.8, 95% CI: 1.1-6.8) and fungal infections (HR 3.26, 95% CI: 1.07-9.9). Conclusions: ACLF is an independent predictor of one-year post-transplantation survival. Importantly, transplant recipients with ACLF require the use of more resources than patients without ACLF.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome defined by an acute deterioration of the liver function associated with extrahepatic organ failures requiring intensive care support and associated with a high short-term mortality. ACLF has emerged as a major cause of mortality in patients with cirrhosis and chronic liver disease. ACLF has a unique pathophysiology in which systemic inflammation plays a key role; this provides the basis of novel therapies, several of which are now in clinical trials. Intensive care unit (ICU) therapy parallels that applied in the general ICU population in some organ failures but has peculiar differential characteristics in others. Critical care management strategies and the option of liver transplantation (LT) should be balanced with futility considerations in those with a poor prognosis. Nowadays, LT is the only life-saving treatment that can radically improve the long-term prognosis of patients with ACLF. This narrative review will provide insights on the current understanding of ACLF with emphasis on intensive care management. [ABSTRACT FROM AUTHOR]

Summary: Liver injury or failure is observed in up to 20% of patients admitted to the intensive care unit and is associated with poor prognosis. Timely recognition and initiation of appropriate management are the most important steps in minimising adverse outcome for patients. Distinguishing between primary or secondary liver failure, and between acute or chronic liver disease aids appropriate management. This can be challenging in cases of limited history and delayed or protracted presentation. Liver failure should be considered as a multisystem disease, with numerous systemic manifestations that must be considered to optimise supportive intensive care unit care. In this narrative review, we summarise an approach to patients with deranged liver biochemistry admitted to a general intensive care unit. We focus on interpretation of patterns of deranged liver biochemistry and the necessary investigations required to identify the related aetiologies. We also propose an evidence‐based approach to the management of liver failure and its extrahepatic manifestations. This review, in addition, clarifies when to seek expert advice or refer patients to a tertiary centre. [ABSTRACT FROM AUTHOR]

Paracentesis-induced circulatory disturbance (PICD) occurs in 12–20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P = 0.851). Midodrine was found to be more cost-effective. Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis. [ABSTRACT FROM AUTHOR]

Studies evaluating the impact of SARS-CoV-2 on chronic liver disease (CLD) are limited and have focused mostly on hospitalized patients or those with cirrhosis. We aim to evaluate the impact of underlying CLD on patient outcomes following COVID-19 using a one of the largest COVID-19+CLD cohorts to date. Data from the COVID-19 Research Database (https://covid19researchdatabase.org) were evaluated from April 1, 2020, to August 31, 2021, to determine whether concurrent CLD was associated with worse outcomes within 30 day of COVID-19 diagnosis, including need for hospitalization, pneumonia, severe pneumonia, respiratory failure, and multiorgan failure. Among patients with COVID-19+CLD, risks of liver decompensation and acute on chronic liver failure (ACLF) were evaluated, stratified by presence of cirrhosis. Adjusted multivariate logistic regression models evaluated the impact of CLD on COVID-19 outcomes. In total, 1,208,905 unique patients with COVID-19 were identified; 44,008 (3.6%) had concurrent CLD, among which 6515 (14.8%) had cirrhosis. Compared to patients without CLD, COVID-19+CLD patients were significantly more likely to require hospitalization (aOR 1.65, 95% CI 1.61–1.69), develop pneumonia (aOR 1.11, 95% CI 1.08–1.14), severe pneumonia (aOR 1.74, 95% CI 1.62–1.86), respiratory failure (aOR 1.14, 95% CI 1.10–1.17), and multiorgan failure (aOR 1.84, 95% CI 1.72–1.97), P < 0.0001 for all. Among COVID-19+CLD patients, underlying cirrhosis was associated with even higher risk of these poor outcomes, and higher risk of acute liver decompensation or ACLF. Among one of the largest studies to date evaluating patients with COVID-19 and CLD, underlying CLD is associated with significantly greater risk of poor outcomes following SARS-CoV-2 infection, particularly among cirrhotic patients. [ABSTRACT FROM AUTHOR]

Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short‐term mortality. Given that ACLF has many different ‘phenotypes’, medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely. [ABSTRACT FROM AUTHOR]

Introduction: Helicobacter pylori (H. pylori) infection is a global healthcare challenge. In its course of infection, Helicobacter pylori infection leads to a systemic increase of post-inflammatory cytokines and can have extra gastric manifestations, affecting the worsening of metabolic and cardiovascular diseases and endangering normal liver function, especially when liver cirrhosis is present. Aim: The aim of this study was to examine the frequency of H. pylori infection in patients with cirrhosis of the liver in stage AD or ACLF. The frequency of antibiotic resistance to clarithromycin and fluoroquinolones was also investigated. Material and methods: A prospective study with 45 patients was conducted which included both sexes. Samples of gastric mucosa were taken from all patients included in the study during the upper endoscopy and were sent to the Institute of Microbiology of the Faculty of Medicine University of Belgrade. A molecular method, Polymerase chain reaction (PCR) was used to detect H. pylori and mutations responsible for resistance to clarithromycin and fluoroquinolones. Results: The presence of H. pylori infection was registered in 15 decompensated patients (33.33%), while 30 (66.67%) were negative. In H. pylori positive patients, PCR detection of genotypes responsible for antibiotic resistance revealed clarithromycin resistance in 11 patients (73.33%), while fluoroquinolone resistance was detected in 7 patients (46.66%). In 6 patients (40.0%), an associated resistance to clarithromycin and fluoroquinolones was found. Conclusion: The H. pylori infection in cirrhotic patients with acute decompensation or ACLF has no significant effect on the severity of the clinical condition, elevated laboratory parameters and survival. Resistance rates to fluoroquinolones and clarithromycin or both antibiotics are high in decompensated patients with cirrhosis. There is a need to increase awareness of the rational use of antibiotics based on further investigations.

Background: The mortality rate in patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) is still very high. Currently, liver support systems are an alternative therapy in bridging liver transplantation. However, its effectiveness in reducing mortality is still controversial when compared to standard medical therapy (SMT). Our study aims to review the efficacy of liver support system compared to standard medical therapy (SMT) among acute liver failure patients without liver transplantation. Method: We conducted systematic literature searching using PubMed/MEDLINE, EBSCO-CINAHL, ProQuest, and Cochrane databases. Selected articles were examined for duplicates and were screened by abstract and title. Then, we appraised the articles based on the critical appraisal tools from Centre for Evidence-Based Medicine (CEBM) University of Oxford Results: One systematic review and meta-analysis of randomized control trials study was extracted after thorough research. Alhamshi et al showed that extracorporeal liver support has significantly reduced mortality in both ALF and ACLF patients as the primary outcome. Other main findings about adverse events including hepatic encephalopathy, thrombocytopenia, bleeding, and infection were still unclear. Conclusion: The use of liver support system demonstrated better outcome in reducing mortality to standard medical therapy in transplant free patients with liver failure, but best modality recommendation was inconclusive.

Administration of prophylactic antibiotics (typically third generation cephalosporins) in ACLF patients with UGIB substantially reduces the occurrence rate of infections and rebleeding as well as improves survival ([3]). Recommendation: We recommend using octreotide or SSA in the treatment of portal hypertensive bleeding in critically ill ACLF patients. Keywords: acute liver failure; acute on chronic liver failure; clinical practice guidelines; Grading Recommendations; Assessment; Development, and Evaluation EN acute liver failure acute on chronic liver failure clinical practice guidelines Grading Recommendations Assessment Development, and Evaluation 653 656 4 04/17/23 20230501 NES 230501 Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are conditions frequently encountered in the ICU and are associated with high mortality. [Extracted from the article]

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence. [ABSTRACT FROM AUTHOR]

We report the case of a 36-year-old male who was referred to us with a provisional diagnosis of ethanol-related acute on chronic liver failure with ascites, encephalopathy, and altered liver function tests (LFTs). The patient underwent a living donor liver transplant. Posttransplant, he had an uneventful recovery till postoperative day (POD) day 7 when he developed tachycardia and low-grade fever. The immunosuppression has to be withheld till POD 26. The patient later developed deranged LFT and an initial liver biopsy showed features of acute cellular rejection. He also had ongoing tachycardia; thus, immunosuppression was withheld. Subsequent to that patient developed rapid progression from progressive early to chronic rejection (CR) within 78 days posttransplant. The patient initially responded to antithymocyte globulin, but finally succumbed to fungal infection. CR usually occurs over 6 months posttransplant. The occurrence of CR was noted very early in the index patients. This case highlights the importance of a basic step-wise approach to a case post liver transplant. It also highlights the importance of specialized liver histopathology aiding in early diagnosis.

Fei Wang,1,&ast; Minghui Tai,1,&ast; Yajuan He,1 Zhen Tian1,2 1Department of Ultrasound, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Tian, Department of Ultrasound, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta Road (w), Xi’an, 710061, People’s Republic of China, Tel +86 186 8290 3901, Fax +86 029 85234641, Email tianzhen@xjtufh.edu.cnBackground and Aim: Fewer than 50% of patients with acute-on-chronic liver failure (ACLF) recover spontaneously, and without liver transplantation, ACLF is associated with high death rates. Nitric oxide (NO) has a role in the pathogenesis of various liver disorders. We investigated if serum NO level could be used as a biomarker to predict the severity and prognosis of patients with ACLF.Methods: Between January 2018 and September 2020, a retrospective cohort of 120 ACLF patients, as well as healthy and cirrhotic controls, was investigated. The serum NO levels were measured using a commercial ELISA kit, and Kaplan–Meier survival analysis was conducted.Results: ACLF patients had significantly higher serum NO levels than healthy and cirrhotic controls. Multivariate analysis indicated that the serum NO level (HR=1.078, 95% CI 1.031– 1.126, P< 0.01), as well as the Model for End-stage Liver Disease (MELD) score, may be an affordable, easily available, and significant independent predictive marker for mortality. In ACLF patients, a serum NO level of > 53.5 μmol/L was associated with a significant increase in the risk of mortality or liver transplantation. A combination of serum NO level and MELD score to assess the severity and prognosis of ACLF patients showed enhanced performance.Conclusion: Based on serum NO levels at the time of hospital admission, ACLF patients may be divided into high-risk and low-risk groups. The combination of serum NO level and MELD score is more closely linked to the patient’s outcome than either value alone. This method might be used to evaluate patient prognoses and select candidates for liver transplantation.Keywords: acute on chronic liver failure, autophagy, nitric oxide, reactive oxygen species, prediction

Abstract Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most prevalent type of ACLF in China. The mortality rate of HBV-ACLF has decreased in recent years due to advances in treatment therapies; however, it is still above 50%. Many cases of HBV-ACLF are caused by HBV reactivation due to discontinuation of nucleoside analog treatment. The present study focused on plasma levels of superoxide dismutase (SOD) in HBV-ACLF patients and investigated whether the plasma level of SOD is a useful biomarker in assessing disease severity and predicting outcomes of HBV-ACLF patients, including patients treated with Entecavir (ETV) and patients who were withdrawn from ETV treatment. Methods Plasma samples and clinical data from 200 HBV-ACLF patients and from age- and sex-matched cirrhotic and healthy controls were collected and analyzed. Plasma levels of SOD were measured using an ELISA commercial kit. Results Among the HBV-ACLF patients, in the ETV withdrawal group, the mortality rate was higher than in the ETV group (69.95% vs 46.71%, P 428 U/mL than in patients with plasma SOD levels ≤ 428 U/mL. Conclusions Reactivation of HBV and elevated oxidative stress caused by discontinuation of ETV treatment are crucial factors in the pathogenesis of HBV-ACLF. Plasma level of SOD may serve as a useful biomarker in estimating disease severity and predicting outcomes of HBV-ACLF patients who stop ETV treatment.

Objective: Management of coagulopathy in chronic liver disease (CLD) poses a challenge for critical care physicians. Prothrombinex®-VF is a low-volume product with rapid onset of action. Evidence for its efficacy and safety in CLD is limited and cases of acute intravascular coagulation and fibrinolysis (AICF) and/or disseminated intravascular coagulation (DIC) have been reported. Our objective was to evaluate the role of Prothrombinex®-VF in reversal of coagulopathy and the incidence AICF/DIC, thromboembolic events and mortality. Methods: This was a retrospective, multi-centre study of Prothrombinex®-VF use in CLD across 11 hospitals over a 2-year period, excluding those on therapeutic anticoagulation. Patients were subclassified into acute on chronic liver failure (ACLF), acute decompensation (ADC) and compensated cirrhosis. Reversal of coagulopathy was defined as international normalised ratio (INR) <1.5 x upper limit normal (ULN), prothrombin time <1.5 x ULN, activated partial thromboplastin time <1.5 x ULN and fibrinogen >1 g/L. Markers of AICF/DIC were recorded. Results: Thirty CLD patients were included, and the median model for end-stage liver disease score was 23.5. Acute bleeding was the most common indication for Prothrombinex®-VF (60%). All had baseline coagulopathy and the majority did not achieve reversal. Key indicators of AICF/DIC were mainly observed in those with ACLF; bleeding from mucosa or lines (53%), worsening hypofibrinogenaemia (60%), worsening thrombocytopaenia (60%). The ADC and compensated cirrhosis groups were relatively unaffected. Incidence of venous thromboembolism was 6%. Overall mortality was 43% and 70% in ACLF. Conclusion: Prothrombinex®-VF did not lead to meaningful reversal of coagulopathy and should be used with caution in CLD. Patients with ACLF were more likely to develop AICF/DIC following Prothrombinex®-VF, although the association is uncertain. Further studies are needed to evaluate the safety and efficacy of Prothrombinex®-VF use in CLD. [ABSTRACT FROM AUTHOR]

Abstract Background Fewer than 50% of patients with acute-on-chronic liver failure (ACLF) recover spontaneously, and ACLF has high mortality without liver transplantation. Oxidative stress has been shown to mediate hepatic inflammation during acute liver failure (ALF). We wanted to see if a biomarker for oxidative stress might be used to measure the severity and prognosis of ACLF patients. Methods A retrospective cohort of 124 ACLF patients, as well as healthy individuals, liver cirrhosis and ALF patients, was studied between January 2015 and September 2018. The levels of plasma superoxide dismutase (SOD) were detected using an ELISA commercial kit, and the Kaplan–Meier method was used for survival analysis. Results Patients with ACLF had statistically higher plasma SOD levels than the controls did (healthy controls and liver cirrhosis patients); however, the levels did not differ from those in patients with ALF. The plasma SOD level may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 1.201, 95% CI 1.001–1.403, P 428 U/mL was linked to a statistically significant increase in the likelihood of death or liver transplantation in ACLF patients. Combination of plasma SOD levels and MELD scores improved performance in measuring the severity and prognosis of ACLF patients. Conclusion Patients with ACLF can be classified into high-risk and low-risk groups based on their plasma SOD levels at the time of admission to the hospital. The patient outcome is more closely connected with the combination of SOD level and MELD score than either value alone. This approach might be used to predict patient prognoses and prioritize liver transplant candidates.

INTRODUCTION: Plasma exchange (PLEX) is one of the experimental modalities of treatment for liver failure. We report our experience of PLEX in patients with acute-(ALF) or acute-on-chronic (ACLF) liver failure. METHODS: Hemodynamically stable adult patients with ALF or ACLF, encephalopathy, model for end-stage liver disease (MELD) score ≥ 15, and clinical worsening/no improvement after 72-h of inpatient care were included. PLEX cycles repeated every 48 h, each of 2.5–4.0 h duration with 1–1.5 times of estimated plasma volume, were given. PLEX cycle was repeated till either of the end-points were achieved (i) MELD < 20 for 48 h or reaches below the baseline, whichever is lower, (ii) completed three PLEX cycles, (iii) hemodynamic instability, (iv) or outcome achieved. Outcome of interest was categorized as favorable (discharged in stable condition) or unfavorable (death or discharge in moribund condition). Data are expressed as median (interquartile range). RESULTS: Sixteen patients (age 35 [27–48] years; male 8; ALF 5, ACLF 11; MELD 33 [27–37]; CLIF-SOFA 10 [8.5–12]) were included. Participants received 2 (1-3) cycles of PLEX during 13 (11–25) days of hospitalization. Overall, serum bilirubin, INR, creatinine, MELD, and CLIF-SOFA scores were significantly improved after PLEX. Five patients (5/16, 31%) had complete resolution of HE. Eight patients (50%) had a favorable outcome. Those with favorable outcome had significant improvement in serum bilirubin, INR, and CLIF-SOFA scores as compared to those with unfavorable outcome. CONCLUSION: PLEX may be effective in patients with ALF or ACLF. More data are needed to establish its role in the management of liver failure.

We report the case of a 36‑year‑old male who was referred to us with a provisional diagnosis of ethanol‑related acute on chronic liver failure with ascites, encephalopathy, and altered liver function tests (LFTs). The patient underwent a living donor liver transplant. Posttransplant, he had an uneventful recovery till postoperative day (POD) day 7 when he developed tachycardia and low‑grade fever. The immunosuppression has to be withheld till POD 26. The patient later developed deranged LFT and an initial liver biopsy showed features of acute cellular rejection. He also had ongoing tachycardia; thus, immunosuppression was withheld. Subsequent to that patient developed rapid progression from progressive early to chronic rejection (CR) within 78 days posttransplant. The patient initially responded to antithymocyte globulin, but finally succumbed to fungal infection. CR usually occurs over 6 months posttransplant. The occurrence of CR was noted very early in the index patients. This case highlights the importance of a basic step‑wise approach to a case post liver transplant. It also highlights the importance of specialized liver histopathology aiding in early diagnosis. [ABSTRACT FROM AUTHOR]

The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert's recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts' statements may help careful patient selection and better treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder, potentially resulting in end-stage liver disease, with a paucity of data on the evolution of cirrhosis., Aims: Our aim was to describe the demographics and mortality in hospitalizations over time in individuals diagnosed with cirrhosis due to alcohol-associated liver disease (ALD) in relation to prior MBS., Methods: We included patients hospitalized at the Ghent University Hospital between 1/1/2010 and 01/09/2023 with cirrhosis due to ALD. Data were retrieved retrospectively from all hospitalizations., Results: 46/275 (16.7%) of individuals with cirrhosis admitted with ALD had a history of MBS; they were predominantly female (76.1%), in contrast to the non-MBS population (29.7%) (p < 0.0001) and were significantly younger at the time of diagnosis (46 vs. 58 years, p < 0.0001). Liver disease evolved at a faster pace in the MBS group with a shorter time to first hospitalization (5 vs. 13 months, p = 0.036), and consecutive hospitalizations. The proportion with primary hospitalization due to acute-on-chronic liver failure (ACLF) was significantly larger in the MBS group (60.9% vs. 27.6%, p < 0.0001), and throughout the following hospitalizations, ACLF remained more prevalent in the MBS group. Modeled transplant-free survival was lower in the MBS group (p = 0.004), with ACLF as the main cause of death. The weekly amount of alcohol consumed during drinking periods and duration of use were significantly lower in the MBS group., Conclusions: MBS patients hospitalized with ALD develop acute decompensation at a faster pace, with more overall ACLF hospitalizations, and higher cumulative mortality, despite being 12 years younger on average., Clinical Trial Registration: Not applicable., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.

Background and Aims: Improvement in the nutritional status of Acute on Chronic Liver Failure(ACLF) patients may lead to reduction in morbidity and mortality. This study assessed the impact of dietician supported outpatient intensive nutrition therapy(OINT) on survival and frailty in patients with alcohol related ACLF METHODS: 70 patients with alcohol related ACLF(Asia Pacific Association for the Study of the Liver, APASL-criteria) and frailty were randomized 1:1 to receive standard medical therapy(SMT) plus OINT(intervention) versus SMT(control) alone. The primary outcome was an improvement in survival at 3 months. Secondary outcome measures included improvement in frailty, prognostic scores and hospitalization., Results: There was a significant improvement in overall survival in the OINT group as compared to SMT after 3 months of follow up, 91.4% (Standard error (SE): 4.7%) vs. 57.1% (SE: 8.4%), P<.00). On cox regression model, inclusion in the intervention arm, baseline Skeletal Muscle Index(SMI), and Asia Pacific Association for the Study of the Liver ACLF Research Consortium(AARC score) were independent predictors of survival (P<.05). The Liver frailty index(LFI) score also significantly improved in the OINT as compared to SMT, Δ-0.93 -(0.71-1.13) vs. Δ -0.33 -(0.44-0.72)(P<.00). The disease severity including MELD, MELD-Na, and AARC score showed a significant improvement in the OINT group as compared to the SMT group(P<.05). The patients in OINT group had lesser number of hospitalizations 6(17%) versus 16(45.7%)(P=.01) as compared to SMT group., Conclusion: Outpatient intensive nutrition therapy significantly improves survival, frailty and disease severity with a reduction in number of hospitalizations and supports the key role of nutrition in treatment of alcohol related ACLF patients., (Copyright © 2024. Published by Elsevier Inc.)

Background: Acute on Chronic Liver Failure (ACLF) complicates chronic liver disease (CLD) combining rapidly progressive hepatic with extra-hepatic multiple organ failure and high short-term mortality. Effective therapeutic options are very limited, and liver transplantation (LT) seldom utilised through concerns of high recipient mortality and resource use. Retrospective reports suggest recent outcomes may have improved, but use of LT for ACLF has not been prospectively assessed., Methods: A prospective programme of prioritised liver graft allocation for selected recipients with ACLF through registration on a new national tier, initiated in May 2021 in all 7 United Kingdom LT centres. Candidates were selected by centre multidisciplinary teams, with inclusion criteria mandating cirrhotic CLD with ACLF requiring critical care (CC) organ support and expected 1-month mortality >50%. Exclusion criteria included age ≥60 years, previous LT, comorbidity or substance misuse profile precluding elective LT. A pilot 50 registrations were planned, with pre-specified futility criteria of a 1-year post-LT survival of 60%., Findings: Fifty-two patients were registered on the ACLF tier, median (IQR) age 46 (39-52) years, ACLF grade 3 (3-3) and Model for End-stage Liver Disease (MELD) 39 (35-40). At registration 32 (62%) required mechanical ventilation, 44 (85%) vasopressors and 46 (89%) renal replacement. Forty-two (81%) underwent LT 2 (2-5) days after registration: 10 (19%) did not. All non-transplanted died at median 7 (4-13) days after registration (p < 0.0001 vs. LT). Post-LT follow-up was 212 (119-530) days and patient survival 81% (95% CI 66-91): 28-, 90-day and 1-year survival after registration 93%, 86% and 77%. Median length of CC and hospital stay in LT recipients was 16 (8-28) and 35 (23-54) days respectively., Interpretation: We report the first prospective national series of prioritised liver transplantation for critically ill patients with ACLF. For selected recipients LT is a practical and highly effective treatment option where no other similarly effective interventions exist., Funding: There was no funding for the study., Competing Interests: WB: Consulting Fees: Sana Biotech/Flagship Pioneering, RT: none, IAR: Consulting Fees: Roche, Novo Nordisk, Boehringer Ingelheim, Honoraria: Norgine, Research Committee Chair, British Association for the Study of the Liver, AC: none, MJA: none, MEDA: Payment or honoraria: GSK: made to CUHFT as part of research collaboration, GW: Support for attending meetings from NHS Blood and Transplant, TP: none, JM: none, LB: none, SM: none, DC: none, BJH: none, RW: none, RJ: Royalties or Licenses: Co-Founder (with stock options): Yaqrit Ltd, Cyberliver Limited, Hepyx, Limited, Payment or honoraria: Grifols, Committee evaluating grants, Patents planned, issued or pending: Patent Families: DIALIVE, CARBALIVE, TLR4 antagonists, Targeting Pyroptosis; Targeting Necroptosis; Ornithine Phenylacetate, KJS: none, JI: none, DT: none., (© 2024 The Authors.)

How to cite this article: Srinivasan A, Prusty BSK. High Altitude Liver Failure: An Infrequent Trigger. Indian J Crit Care Med 2024;28(10):988., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)